Technical Abstract:
Necrotizing enterocolitis (NEC) is a major complication of enteral feeding in premature infants with a high morbidity and mortality. Early enteral feeding of fortified human milk is considered optimal nutrition for the preterm infant. However, human milk is not always available, and commercial formulas are needed that mimic human milk as closely as possible. Our aim was to test the effects of early vs. late enteral feeding of an intact vs. partially hydrolyzed protein formula on NEC incidence in a preterm piglet model being developed to closely simulate clinical practice. Moderately preterm pigs (at 90% of gestation) were randomized to either an early (EA) or late (LA) feeding protocol. The EA and LA groups received 2 d and 5 d of total parenteral nutrition (TPN), and orogastric formula feeds (50% full intake) began on d of life 3 and 6, respectively, and PN continued. Pigs in the EA and LA groups also were randomized to one of two formulas containing either intact or hydrolyzed protein. All four groups were euthanized due to NEC onset or after 5 d formula feeding. NEC severity and incidence was assessed based on macroscopic and histological scoring in the stomach, proximal jejunum, distal ileum, and colon. Nineteen of 25 pigs in the EA group developed NEC (76%) as compared to 9 of 22 pigs in the LA group (41%) (p = 0.02). The mean total clinical NEC severity score was significantly greater in the early vs. late group (11.08 vs. 6.55; p = 0.004). There was no significant difference in the incidence of NEC in pigs that received hydrolyzed protein formula (75% in EA, 45% in LA) and those that received intact protein formula (77% in EA, 34% in LA). In conclusion, although TPN has been associated with impaired gut development, this study provides evidence that delayed initiation of enteral feeding at 5 d vs. 2 d is protective and reduced both the incidence and severity of NEC in preterm pigs. The formula containing intact or hydrolyzed protein had no effect on NEC development. Future studies will explore whether a more gradual introduction of feeds impacts NEC incidence.